Formation of regulatory modules by local sequence duplication

Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of neighboring transcription factor binding sites in the fly genome have formed from a common sequence origin by local duplications. This mode of evolution is found to produce regulatory information: duplications can seed new sites in the neighborhood of existing sites. Duplicate seeds evolve subsequently by point mutations, often towards binding a different factor than their ancestral neighbor sites. These results are based on a statistical analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome, and a comparison set of intergenic regulatory sequence in Saccharomyces cerevisiae. In fly regulatory modules, pairs of binding sites show significantly enhanced sequence similarity up to distances of about 50 bp. We analyze these data in terms of an evolutionary model with two distinct modes of site formation: (i) evolution from independent sequence origin and (ii) divergent evolution following duplication of a common ancestor sequence. Our results suggest that pervasive formation of binding sites by local sequence duplications distinguishes the complex regulatory architecture of higher eukaryotes from the simpler architecture of unicellular organisms

Co-occurrence of outlet impingement syndrome of the shoulder and restricted range of motion in the thoracic spine - a prospective study with ultrasound-based motion analysis

<p>Abstract</p> <p>Background</p> <p>Shoulder complaints, and especially the outlet-impingement syndrome, are a common condition. Among other things, poor posture has been discussed as a cause. A correlation between impingement syndrome and restricted mobility of the thoracic spine (T) has been described earlier, but there has been no motion analysis of the thoracic spine to show these correlations. In the present prospective study, we intended to find out whether there is a significant difference in the thoracic sagittal range of motion (ROM) between patients with a shoulder outlet impingement syndrome and a group of patients who had no shoulder pathology. Secondly, we wanted to clarify whether Ott's sign correlates with ultrasound topometric measurements.</p> <p>Methods</p> <p>Two sex- and age-matched groups (2 × n = 39) underwent a clinical and an ultrasound topometric examination. The postures examined were sitting up straight, sitting in maximal flexion and sitting in maximal extension. The disabilities of the arm, shoulder and hand (DASH) score (obtained by means of a self-assessment questionnaire) and the Constant score were calculated. Lengthening and shortening of the dorsal projections of the spine in functional positions was measured by tape with Ott's sign.</p> <p>Results</p> <p>On examination of the thoracic kyphosis in the erect seated posture there were no significant differences between the two groups (p = 0.66). With ultrasound topometric measurement it was possible to show a significantly restricted segmental mobility of the thoracic spine in the study group compared with the control group (p = 0.01). An in-depth look at the mobility of the subsegments T1-4, T5-8 and T9-12 revealed that differences between the groups in the mobility in the lower two sections of the thoracic spine were significant (T5-8: p = 0.03; T9-12: p = 0.02). The study group had an average Constant score of 35.1 points and the control group, 85.5 (p < 0.001). On the DASH score the patient group reached 34.2 points and the control group, 1.4 (p < 0.001). The results of Ott's sign differed significantly between the two collectives (p = 0.0018), but showed a weak correlation with the ultrasound topometric measurements (study group flexion/extension: r = 0.36/0.43, control group flexion/extension: r = 0.29/0.26).</p> <p>Conclusion</p> <p>The mobility of the thoracic spine should receive more attention in the diagnosis and therapy of patients with shoulder outlet impingement syndrome.</p

Holographic Conductivity in Disordered Systems

The main purpose of this paper is to holographically study the behavior of conductivity in 2+1 dimensional disordered systems. We analyze probe D-brane systems in AdS/CFT with random closed string and open string background fields. We give a prescription of calculating the DC conductivity holographically in disordered systems. In particular, we find an analytical formula of the conductivity in the presence of codimension one randomness. We also systematically study the AC conductivity in various probe brane setups without disorder and find analogues of Mott insulators.Comment: 43 pages, 28 figures, latex, references added, minor correction

Strong-coupling expansion and effective hamiltonians

When looking for analytical approaches to treat frustrated quantum magnets, it is often very useful to start from a limit where the ground state is highly degenerate. This chapter discusses several ways of deriving {effective Hamiltonians} around such limits, starting from standard {degenerate perturbation theory} and proceeding to modern approaches more appropriate for the derivation of high-order effective Hamiltonians, such as the perturbative continuous unitary transformations or contractor renormalization. In the course of this exposition, a number of examples taken from the recent literature are discussed, including frustrated ladders and other dimer-based Heisenberg models in a field, as well as the mapping between frustrated Ising models in a transverse field and quantum dimer models.Comment: To appear as a chapter in "Highly Frustrated Magnetism", Eds. C. Lacroix, P. Mendels, F. Mil

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Genome Erosion in a Nitrogen-Fixing Vertically Transmitted Endosymbiotic Multicellular Cyanobacterium

Background: An ancient cyanobacterial incorporation into a eukaryotic organism led to the evolution of plastids (chloroplasts) and subsequently to the origin of the plant kingdom. The underlying mechanism and the identities of the partners in this monophyletic event remain elusive. Methodology/Principal Findings: To shed light on this evolutionary process, we sequenced the genome of a cyanobacterium residing extracellularly in an endosymbiosis with a plant, the water-fern Azolla filiculoides Lam. This symbiosis was selected as it has characters which make it unique among extant cyanobacterial plant symbioses: the cyanobacterium lacks autonomous growth and is vertically transmitted between plant generations. Our results reveal features of evolutionary significance. The genome is in an eroding state, evidenced by a large proportion of pseudogenes (31.2%) and a high frequency of transposable elements (,600) scattered throughout the genome. Pseudogenization is found in genes such as the replication initiator dnaA and DNA repair genes, considered essential to free-living cyanobacteria. For some functional categories of genes pseudogenes are more prevalent than functional genes. Loss of function is apparent even within the ‘core’ gene categories of bacteria, such as genes involved in glycolysis and nutrient uptake. In contrast, serving as a critical source of nitrogen for the host, genes related to metabolic processes such as cell differentiation and nitrogen-fixation are well preserved. Conclusions/Significance: This is the first finding of genome degradation in a plant symbiont and phenotypically complex cyanobacterium and one of only a few extracellular endosymbionts described showing signs of reductive genome evolution. Our findings suggest an ongoing selective streamlining of this cyanobacterial genome which has resulted in an organism devoted to nitrogen fixation and devoid of autonomous growth. The cyanobacterial symbiont of Azolla can thus be considered at the initial phase of a transition from free-living organism to a nitrogen-fixing plant entity, a transition process which may mimic what drove the evolution of chloroplasts from a cyanobacterial ancestor

The Calcitonin Receptor Gene Is a Candidate for Regulation of Susceptibility to Herpes simplex Type 1 Neuronal Infection Leading to Encephalitis in Rat

Herpes simplex encephalitis (HSE) is a fatal infection of the central nervous system (CNS) predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s) regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL), Hse1, on rat chromosome 4 (confidence interval 24.3–31 Mb; LOD score 29.5) governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr) as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development

A Key Marine Diazotroph in a Changing Ocean: The Interacting Effects of Temperature, CO2 and Light on the Growth of Trichodesmium erythraeum IMS101

Trichodesmium is a globally important marine diazotroph that accounts for approximately 60-80% of marine biological N2 fixation and as such plays a key role in marine N and C cycles. We undertook a comprehensive assessment of how the growth rate of Trichodesmium erythraeum IMS101 was directly affected by the combined interactions of temperature, pCO2 and light intensity. Our key findings were: low pCO2 affected the lower temperature tolerance limit (Tmin) but had no effect on the optimum temperature (Topt) at which growth was maximal or the maximum temperature tolerance limit (Tmax); low pCO2 had a greater effect on the thermal niche width than low-light; the effect of pCO2 on growth rate was more pronounced at suboptimal temperatures than at supraoptimal temperatures; temperature and light had a stronger effect on the photosynthetic efficiency (Fv/Fm) than did CO2; and at Topt, the maximum growth rate increased with increasing CO2, but the initial slope of the growth-irradiance curve was not affected by CO2. In the context of environmental change, our results suggest that the (i) nutrient replete growth rate of Trichodesmium IMS101 would have been severely limited by low pCO2 at the last glacial maximum (LGM), (ii) future increases in pCO2 will increase growth rates in areas where temperature ranges between Tmin to Topt, but will have negligible effect at temperatures between Topt and Tmax, (iii) areal increase of warm surface waters (> 18°C) has allowed the geographic range to increase significantly from the LGM to present and that the range will continue to expand to higher latitudes with continued warming, but (iv) continued global warming may exclude Trichodesmium spp. from some tropical regions by 2100 where temperature exceeds Topt

Male urine signals social rank in the Mozambique tilapia (Oreochromis mossambicus)

<p>Abstract</p> <p>Background</p> <p>The urine of freshwater fish species investigated so far acts as a vehicle for reproductive pheromones affecting the behaviour and physiology of the opposite sex. However, the role of urinary pheromones in intra-sexual competition has received less attention. This is particularly relevant in lek-breeding species, such as the Mozambique tilapia (<it>Oreochromis mossambicus</it>), where males establish dominance hierarchies and there is the possibility for chemical communication in the modulation of aggression among males. To investigate whether males use urine during aggressive interactions, we measured urination frequency of dye-injected males during paired interactions between size-matched males. Furthermore, we assessed urinary volume stored in the bladder of males in a stable social hierarchy and the olfactory potency of their urine by recording of the electro-olfactogram.</p> <p>Results</p> <p>Males released urine in pulses of short duration (about one second) and markedly increased urination frequency during aggressive behaviour, but did not release urine whilst submissive. In the stable hierarchy, subordinate males stored less urine than males of higher social rank; the olfactory potency of the urine was positively correlated with the rank of the male donor.</p> <p>Conclusion</p> <p>Dominant males store urine and use it as a vehicle for odorants actively released during aggressive disputes. The olfactory potency of the urine is positively correlated with the social status of the male. We suggest that males actively advertise their dominant status through urinary odorants which may act as a 'dominance' pheromone to modulate aggression in rivals, thereby contributing to social stability within the lek.</p